Brocco-SGS: Cancer Research Review

Bladder, Colon , Liver, Lung, Breast, Stomach, Prostate, Skin and Tumor Blocking

An amazing compound found in 3-7 day old broccoli sprouts, Sulforaphane glucosinolate (SGS) can protect us and our companion animals against cancer.


Sulforaphane increases the body's own defense system against carcinogens. Cells in the body contain a family of detoxification enzymes (Phase 2 enzymes) that neutralize cancer-causing chemicals as well as free radicals before they damage DNA and initiate cancer.


"Chemoprotection is a deliberate effort to increase the body^s defense systems against chemicals, including carcinogens, that can lead to disease," according to John Hopkins University Professor Dr. Talalay. "Chemoprotection may lower a person^s risk of developing cancer by building up the body^s own defenses, particularly through diet." Dr. Talalay^s research promotes chemo-protection that can be accomplished by activating the body's Phase 2 "defense" The Phase Two enzymes are an integral part of the body^s amazing detoxification system, neutralizing carcinogens and making them inactive. This detoxification system turns carcinogens and other toxic substances into harmless molecules that are excreted from the body.

 

READ: Broccoli Sprouts, cancer prevention and detoxification

 

BROCCOLI SPROUTS pack powerful SGS

 

Broccoli sprouts are a concentrated source of cancer-fighting sulforaphane.
In September 1997, a group of scientists at the Johns Hopkins University School of Medicine made a breakthrough discovery: broccoli sprouts contain ten to one hundred times more sulforaphane than mature broccoli.(1)

(1)Fahey, J.W., Zhang, Y., Talalay, P. Broccoli sprouts: An exceptionally rich source of inducers of enzymes that protect against chemical carcinogens. Proc. Natl. Acad. Sci. 1997; 94:10367-10372.

CANCER RESEARCH REVIEW: Broccoli's Sprouts.

Positive research is coming in, from human and animal studies for a wide range of cancers: Bladder, Breast, Colon, Liver, Lung, Prostate, Skin.

BLADDER CANCER


Scientists at Ohio State University published a study that showed compounds from broccoli were able to decrease progression of cancer in lines of bladder cancer cells from humans and mice. Steven Schwartz and his team used phytochemicals from broccoli and converted them to their active compounds such as sulforaphane. This work builds on previously reported epidemiological analysis from Harvard and Ohio State that found men who ate 2 or more half-cup servings of broccoli per week had a 44% lower incidence of bladder cancer compared to men who ate less than one serving each week. We do not yet have a citation for the above study, but following are a few additional studies.

1. The role of c-Jun in the AP-1 activation induced by naturally occurring isothiocyanates Food Chem Toxicol. 2005 Sep;43(9):1373-80.Li J, Yao S, Zhang Y. doi:10.1016/j.fct.2005.03.011

2. Dietary isothiocyanates inhibit the growth of human bladder carcinoma cells. J Nutr. 2004 Aug;134(8):2004-10Tang L, Zhang Y. PubMed ID: 15284390

3. Isothiocyanates in the chemoprevention of bladder cancer.  Curr Drug Metab. 2004 Apr;5(2):193-201.Tang L, Zhang Y. PubMed ID: 15078196

BREAST CANCER
One of the critical factors that determines the capacity of a carcinogen to cause cancer is its ability to bind to DNA. This Carcinogen-DNA binding, or adduct formation, causes DNA mutations when the DNA is replicated during cell division. Most of these mutations are never seen and result in cell death. But a very small percentage can result in uncontrolled growth that may lead to cancer. In a paper published in Cancer Letters, a research group at the University of Illinois showed that sulforaphane significantly reduces the formation of these carcinogen-DNA adducts.


1. Broccoli sprouts: An exceptionally rich source of inducers of enzymes that protect against chemical carcinogens.(Proc. Natl. Acad. Sci. USA, Vol. 94, pp. 10367-10372, September 16, 1997. Jed W. Fahey, Yuesheng Zhang, and Paul Talalay PubMed ID: 9294217

2. Inhibition of benzo[a]pyrene- and 1,6-dinitropyrene-DNA adduct formation in human mammary epithelial cells by dibenzoylmethane and sulforaphane.  Cancer Letters 2000 July 3; 155(1):47-54.Singletary K, MacDonald C. PubMed ID: 10814878 Proc. Natl. Acad. Sci. USA, Vol. 94, pp. 10367-10372, September 16, 1997.Jed W. Fahey, Yuesheng Zhang, and Paul Talalay PubMed ID: 9294217

3. Anticarcinogenic Activities of Sulforaphane and Structurally Related Synthetic Norbornyl Isothiocyanates (#) Proc Natl Acad Sci USA 1994 Apr 12;91(8):3147-50 Y Zhang, TW Kensler, C Cho, GH Posner and P Talalay PubMed ID: 8159717

COLON CANCER


Researchers at the American Health Foundation, Valhalla, NY, showed that sulforaphane significantly inhibited the formation of colon cancer in rats. These findings provide the first evidence that sulforaphane plays an important role in preventing colon cancer.

1. Sulforaphane inhibits histone deacetylase in vivo and suppresses tumorigenesis in Apcmin mice.
FASEB Journal Express. Published online January 11, 2006.  Melinda C. Myzak, W. Mohaiza Dashwood, Gayle A. Orner, Emily Ho, and Roderick H. Dashwood doi:10.1096/fj.05-4785fje PubMed ID: 16407454

2. Chemoprevention of colonic aberrant crypt foci in Fischer rats by major isothiocyanates in watercress and broccoli.
Proceedings of the American Association for Cancer Research, March 2000; 41:660. Chung F-L, Conaway CC, Rao CV, Reddy BS. PubMed ID: 11133820

3.Sulforaphane, A Naturally Occurring Isothiocyanate, Induces Cell Cycle Arrest and Apoptosis in HT29 Human Colon Cancer Cells
Cancer Research. 2000 March 1; 60(5):1426-1433.
Gamet-Payrastre L, Li P, Lumeau S, Cassar G, Dupont MA, Chevolleau S, Gase N, Tulliez J, Terrry F. PubMed ID: 10728709


The Johns Hopkins research to date has shown that sulforaphane can protect against cancer. These studies have indicated that the mechanism for this protection is the stimulation of the body^s own antioxidant system. This system, comprised of what we call Phase 2 Enzymes, eliminates carcinogens from the body before they can cause DNA damage. However, what would happen if some of the carcinogens get through this system and actually cause DNA damage or mutations? The answer may lie in a paper published in the prestigious journal, Cancer Research. (March 2000) This paper, published by a French research team, shows for the first time that sulforaphane may be able to do more than just activate antioxidants. This important new research describes the ability of sulforaphane to cause cancer cells to self-destruct (programmed cell death or apoptosis.) The multidimensional ability of sulforaphane to remove carcinogens AND kill cells with potential cancer causing mutations is a major breakthrough in our understanding of this chemoprotectant.

LIVER


In a rural area of China where there is a very high prevalence of liver cancer due to a confluence of hepatitis virus and environmental toxins, scientists at Johns Hopkins University and Qidong Liver Institute PRC, near Shanghai performed experiments to measure the ability of broccoli sprouts to increase the body's abilities to detoxify carcinogens. In a single-blinded placebo-controlled trial, (100 test, 100 control) subjects drank a hot water extract of 3-day-old broccoli sprouts or a placebo, daily for two weeks. The subjects' urine was tested to measure detoxification capacity. The broccoli sprouts test group showed a significant reduction in aflatoxin-DNA adduct levels with increasing levels of broccoli sprout consumption. The change in these biomarkers strongly suggests that there was an enhanced detoxification (neutralization) of carcinogens from the human body leading to a reduction in cancer risk.

1. Effects of glucosinolate-rich broccoli sprouts on urinary levels of aflatoxin-DNA adducts and phenanthene tetraols in a randomized clinical trial in He Zuo Township, Qidong, PRC
Cancer Epidemiol. Biomarkers Prev., Nov 2005; 14(11).
Kensler, T.W., Chen, J-G., Egner, P.A., Fahey, J.W., Jacobson, L.P., Stephenson, K.K., Ye, X., Coady, J.L.,Wang, J-B., Wu, Y., Sun, Y., Zhang, Q-N., Zhang, B-C., Zhu, Y-R., Qian, G-S., Carmella, S.G., Hecht, S.S., Benning, L., Gange, S.J., Groopman, J.D. and Talalay, P. PubMed ID: 16284385

LUNG CANCER


In the September 15, 2005 issue of Cancer Research, scientists from the Georgetown University Medical Center, reported that sulforaphane and another isothiocyanate could prevent benign tumors produced by a cigarette carcinogen from developing into full-blown cancer tumors in lungs of mice. By using a model in which the animals were exposed to the carcinogens before administration of the chemoprotective agent, they demonstrated that the agent (sulforaphane) inhibits the progression of the disease by reducing proliferation and causing apoptosis - programmed cell death of the damaged cells. These findings suggest that chemoprotective agents might be useful among populations that have already been exposed to tobacco carcinogens. This might be useful, for example, as chemoprotective agents for current smokers, ex-smokers, or those exposed to second-hand smoke.
1.Antimetastatic activity of Sulforaphane. Life Science 2006 May 22; 78(26):3043-50.Thejass P, Kuttan G. doi:10.1016/j.lfs.2005.12.038 PubMed ID: 16600309

2. N-Acetylcysteine Conjugate of Phenethyl Isothiocyanate Enhances Apoptosis in Growth-Stimulated Human Lung Cells.
Cancer Res. 2005 Sep 15;65(18):8538-47.
Yang-Ming Yang, Meena Jhanwar-Uniyal, Joel Schwartz, C. Clifford Conaway, H. Dorota Halicka, Frank Traganos and Fung-Lung Chung. PubMed ID: 16166335

3. Phenethyl Isothiocyanate and Sulforaphane and their N-Acetylcysteine Conjugates Inhibit Malignant Progression of Lung Adenomas Induced by Tobacco Carcinogens in A/J Mice. Cancer Res. 65: (18) 8548-8557.
Conaway, C, Wang, C-X, Pittman, B, Yang, Y-M, Schwartz, J, Tian, D, McIntee, E,Hecht, S, Chung, F-L. PubMed ID: 16166336

PROSTATE CANCER


Potent Induction of Phase 2 Enzymes in Human Prostate Cells by Sulforaphane.
Cancer Epidemiology, Biomarkers & Prevention, Vol. 10, pp. 949-954. Sept. 2001.
James D. Brooks, Vincent G. Paton and Genevieve Vidanes.
PubMed ID: 11535546


Human prostate cancer cells responded well to treatment with sulforaphane in the form of broccoli sprout extracts, showing dramatic increases in their Phase 2 protective enzymes. In his article, Dr. James D. Brooks of the Urology Department at Stanford University suggests, "Intervention trials may be warranted [in humans], and broccoli sprouts, a rich natural source of sulforaphane, may be appropriate for use in such a trial."

SKIN CANCER


In a study from Johns Hopkins, mice were exposed to damaging levels of UV light for a period of 20 weeks. Following this, sulforaphane was applied topically to the test group for 11 weeks and compared to untreated controls. At the conclusion of the test, 100% of the control group had tumors. Number of mice with tumors, number of tumors per mouse, and mass of tumors were all reduced by about 50% in the animals that received the broccoli sprout extract. This protocol mirrors the situation of humans exposed to a great deal of sun during childhood, and lower exposure in later life. The significance of this work is that application of the chemoprotective agent was given after exposure to the carcinogen, thus suggesting its ability to prevent progression to of cancer. (Further the test was designed to prevent any "sunscreen" effect of the blocking of the UV radiation thus ensuring that the results could be attributed to the detoxifying protective effects of the broccoli sprout extracts.)


This is the first experiment in which protection was shown against a physical cancer initiator - UV light. Thus, topical application of sulforaphane-containing broccoli sprout extracts is a promising strategy for protecting against skin tumor formation after exposure to UV radiation.


1. Protection against UV-light-induced skin carcinogenesis in SKH-1 high-risk mice by sulforaphane-containing broccoli sprout extracts.
Cancer Epidemiology, Biomarkers & Prevention, November 2005, Vol. 14(11).  Dinkova-Kostova, A, Jenkins, S, Fahey, J, Ye, L, Wehage, S, Liby, K, Stephenson, K, Wade, K and Talalay, P. doi:10.1016/j.canlet.2005.09.012 PubMed ID: 16271437

STOMACH CANCER


In a study from Japan, broccoli sprouts were fed to patients infected with Helicobacter pylori bacteria. H. pylori infection can cause stomach ulcers and markedly increases the risk of developing stomach cancer. After eating 100 grams (3 1/2 ounces) broccoli sprouts daily for 2 months, measures of H. pylori infection were substantially reduced. Control subjects fed a vegetable with no sulforaphane or related compounds showed no change, suggesting strongly that the content of sulforaphane glucosinolate (SGS) in broccoli sprouts was responsible for the reduction of the bacteria.


This confirms test-tube and rodent studies, and a preliminary clinical study on the potent and selective antibacterial properties of sulforaphane and its ability to selectively target the H. pylori bacteria, which are often difficult to eradicate.


"These data strongly suggest that a diet rich in sulforaphane glucosinolate may help protect against gastric cancer, presumably by activating gastric mucosal antioxidant enzymes that can protect the cells from H. pylori-induced DNA damage," stated Dr. Akinori Yanaka of the University of Tsukuba in Japan, lead author of the study.

1.  Daily Intake of Sulforaphane-Rich Broccoli Sprouts Improves Gastritis in H.pylori-Infected Human Subjects. Cancer Epidemiology, Biomarkers & Prevention, November 2005, Vol. 14(11 Part 2): 2754s. Yanaka, A, Zhang, S, Yamamoto, M, Fahey, J.

2.  Oral Broccoli Sprouts for the Treatment of Helicobacter pylori Infection: A Preliminary Report Digestive Diseases and Sciences, 49(7/8):1088-1090, 2004.  Mark V. Galan, Md, Arfana A. Kishan, Md, And Ann L. Silverman, Md doi:10.1023/B:DDAS.0000037792.04787.8a PubMed ID: 15387326

3. Sulforaphane inhibits extracellular, intracellular, and antibiotic-resistant strains of Helicobacter pylori and prevents benzo[a]pyrene-induced stomach tumors.
Proc. Natl. Acad. Sci. USA, Vol. 99, Issue 11, pp. 7610-7615, May 28, 2002
Jed W. Fahey, Xavier Haristoy, Patrick M. Dolan, Thomas W. Kensler, Isabelle Scholtus, Katherine K. Stephenson, Paul Talalay, and Alain Lozniewski  doi:10.1073/pnas.112203099 PubMed ID: 12032331

A Johns Hopkins University research team led by Dr. Jed Fahey, discovered that sulforaphane kills Helicobacter pylori, the bacterium responsible for the vast majority of stomach ulcers and stomach cancers, a leading cause of cancer death worldwide. In their laboratory experiments, the scientists discovered that purified sulforaphane even killed helicobacter that was resistant to commonly-used antibiotics. They also showed that sulforaphane can kill the bacterium whether it is inside or outside cells. In humans, cells lining the stomach can act as reservoirs of helicobacter, making it more difficult to eradicate the infection. Though the pure compound kills helicobacter efficiently, a number of studies are underway to determine whether dietary sources of sulforaphane (broccoli or broccoli sprouts, for instance) have similar effects.

READ: New York Times articles on broccoli sprouts research.

 

Broccoli Sprouts (SGS) Blocks Tumors in Animals

Dr. Talalay^s research at John Hopkins University, tested the sulforaphane in animals. This research found that sulforaphane blocked the formation of mammary tumors in rats treated with a potent carcinogen: The number of rats that developed tumors was reduced by as much as 60%, the number of tumors in each animal was reduced by 80%, and the size of the tumors that did develop was reduced by 75%.

The tumors' appearance was delayed and they grew more slowly. Most recently, researchers from the U.S. and Europe have further examined the effects of SGS in cancer models. Scientists at the American Health Foundation discovered that sulforaphane inhibited the formation of premalignant lesions in the colons of rats. Researchers in Toulouse, France found that sulforaphane induced cell death in human colon carcinoma cells. (http://www.fasebj.org/cgi/content/abstract/05-4785fjev1)

This study suggests that "in addition to the activation of detoxifying enzymes, induction of apoptosis [cell death] is also involved in the sulforaphane-associated chemoprevention of cancer." These results have not yet been validated in humans.

 

READ: Chemoprevention of colonic aberrant crypt foci in Fischer rats by sulforaphane and phenethyl isothiocyanate.